Zif268 and Fos-like immunoreactivity in tetanus toxin-induced epilepsy: reciprocal changes in the epileptic focus and the surround.
Altered gene expression for a number of molecules has been suggested as one of the underlying mechanisms of epileptogenesis. Changes in expression of the immediate early genes, zif268 and c-fos, were investigated in chronic focal epilepsy induced by tetanus toxin (TT, 20-35 ng) injected in the rat motor cortex. Most rats injected with TT and perfused on postoperative day 5, 7 or 14 had recurrent focal seizures after a latent period of 4-13 days, and showed enhanced Zif268 immunoreactivity in a cluster of neurons at the injection site, as well as reduced Zif268 immunoreactivity in a distinct cortical zone around this cluster. C-fos or Fos-related immunoreactivity was decreased over widespread areas of frontoparietal and piriform cortex in epileptic rats, except for a focus at the injection site which, in most cases, showed increases in Fos-like immunoreactivity. Some epileptic rats showed increased Zif268 immunoreactivity in neurons of the ipsilateral ventral lateral and central lateral thalamic nuclei and increased Zif268 and Fos-like immunoreactivity in the pontine nuclei. Rats perfused before onset of seizures, showed no overt changes other than a slight decrease in Zif268 and Fos-like immunoreactivity at the injection site. The reciprocal changes in Zif268 immunoreactive neurons in the epileptic focus and the immediate surround parallel changes in gene expression for a number of molecules important in epileptogenesis and suggest a state of functional disconnection of the epileptic focus from other cortical areas that may contribute to the development and maintenance of focal epilepsy.
Liang
F
F
Department of Anatomy and Neurobiology, University of California, Irvine 92697-1280, USA.
Jones
E G
EG
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D051766:Early Growth Response Protein 1; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D017781:Genes, Immediate-Early / Q000502:physiology; D017874:Immediate-Early Proteins; D008297:Male; D008845:Microinjections; D009044:Motor Cortex / Q000737:chemistry / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D051381:Rats; D013744:Tetanus Toxin; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D013744:Tetanus Toxin; D014157:Transcription Factors